TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8959	27100;27101;27102	chr2:178713259;178713258;178713257	chr2:179577986;179577985;179577984
N2AB	8642	26149;26150;26151	chr2:178713259;178713258;178713257	chr2:179577986;179577985;179577984
N2A	7715	23368;23369;23370	chr2:178713259;178713258;178713257	chr2:179577986;179577985;179577984
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-75
• Domain position: 34
• Structural Position: 48
• Q(SASA): 0.1291
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
W/L	None	None	0.477	D	0.819	0.755	0.942273410946	gnomAD-4.0.0	6.84813E-07	None	None	None	None	N	None	2.98864E-05	0	None	0	0	None	0	0	0	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
W/A	0.9912	likely_pathogenic	0.993	pathogenic	-2.969	Highly Destabilizing	0.547	D	0.839	deleterious	None	None	None	None	N
W/C	0.9931	likely_pathogenic	0.996	pathogenic	-1.463	Destabilizing	0.013	N	0.764	deleterious	D	0.702601123	None	None	N
W/D	0.9994	likely_pathogenic	0.9995	pathogenic	-3.084	Highly Destabilizing	0.981	D	0.873	deleterious	None	None	None	None	N
W/E	0.9993	likely_pathogenic	0.9994	pathogenic	-2.974	Highly Destabilizing	0.981	D	0.877	deleterious	None	None	None	None	N
W/F	0.643	likely_pathogenic	0.6353	pathogenic	-1.691	Destabilizing	0.945	D	0.8	deleterious	None	None	None	None	N
W/G	0.9744	likely_pathogenic	0.9811	pathogenic	-3.199	Highly Destabilizing	0.864	D	0.827	deleterious	D	0.718650844	None	None	N
W/H	0.9951	likely_pathogenic	0.9962	pathogenic	-1.974	Destabilizing	0.995	D	0.842	deleterious	None	None	None	None	N
W/I	0.9621	likely_pathogenic	0.9682	pathogenic	-2.091	Highly Destabilizing	0.894	D	0.877	deleterious	None	None	None	None	N
W/K	0.9995	likely_pathogenic	0.9997	pathogenic	-2.066	Highly Destabilizing	0.945	D	0.873	deleterious	None	None	None	None	N
W/L	0.9123	likely_pathogenic	0.927	pathogenic	-2.091	Highly Destabilizing	0.477	N	0.819	deleterious	D	0.693112732	None	None	N
W/M	0.9868	likely_pathogenic	0.99	pathogenic	-1.56	Destabilizing	0.995	D	0.791	deleterious	None	None	None	None	N
W/N	0.9988	likely_pathogenic	0.9991	pathogenic	-2.708	Highly Destabilizing	0.945	D	0.888	deleterious	None	None	None	None	N
W/P	0.9986	likely_pathogenic	0.9987	pathogenic	-2.411	Highly Destabilizing	0.981	D	0.887	deleterious	None	None	None	None	N
W/Q	0.9994	likely_pathogenic	0.9996	pathogenic	-2.596	Highly Destabilizing	0.981	D	0.874	deleterious	None	None	None	None	N
W/R	0.9984	likely_pathogenic	0.9988	pathogenic	-1.745	Destabilizing	0.975	D	0.885	deleterious	D	0.718852648	None	None	N
W/S	0.9867	likely_pathogenic	0.9904	pathogenic	-2.906	Highly Destabilizing	0.864	D	0.867	deleterious	D	0.718852648	None	None	N
W/T	0.9918	likely_pathogenic	0.9939	pathogenic	-2.728	Highly Destabilizing	0.894	D	0.823	deleterious	None	None	None	None	N
W/V	0.9588	likely_pathogenic	0.9659	pathogenic	-2.411	Highly Destabilizing	0.809	D	0.862	deleterious	None	None	None	None	N
W/Y	0.9068	likely_pathogenic	0.9176	pathogenic	-1.493	Destabilizing	0.981	D	0.804	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.